HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer.

AbstractPURPOSE:
Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, with mutations in PIK3CA being the most common. This study investigated the association between PIK3CA genotype and pathologic complete response (pCR) rates in human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either dual or single anti-HER2 treatment in addition to neoadjuvant chemotherapy.
PATIENTS AND METHODS:
PIK3CA mutations in 504 tumor samples from participants in the neoadjuvant GeparQuattro, GeparQuinto, and GeparSixto studies were evaluated. All HER2-positive patients received either trastuzumab or lapatinib or the combination plus anthracycline-taxane chemotherapy. PIK3CA mutations were evaluated in formalin-fixed, paraffin-embedded tissues from core biopsies with a tumor cell content of ≥ 20% by using classical Sanger sequencing of exon 9 and exon 20.
RESULTS:
Overall, 21.4% of the patients harbored a PIK3CA mutation. Detection of a PIK3CA mutation was significantly associated with a lower pCR rate (19.4% with PIK3CA mutation v 32.8% with PIK3CA wild-type; odds ratio [OR], 0.49; 95% CI, 0.29 to 0.83; P = .008). In the 291 hormone receptor (HR) -positive tumors, pCR rate was 11.3% with a PIK3CA mutation compared with 27.5% with PIK3CA wild-type (OR, 0.34; 95% CI, 0.15 to 0.78; P = .011). In 213 patients with HR-negative tumors, pCR rate was 30.4% with PIK3CA mutation and 40.1% without (OR, 0.65; 95% CI, 0.32 to 1.32; P = .233; interaction test P = .292). In multivariable analysis, HR status and PIK3CA status provided independent predictive information. In patients with PIK3CA mutation, the pCR rates were 16%, 24.3%, and 17.4% with lapatinib, trastuzumab, and the combination, respectively (P = .654) and in the wild-type group, they were 18.2%, 33.%, and 37.1%, respectively (P = .017). Disease-free survival and overall survival were not statistically significantly different between patients with mutant and wild-type PIK3CA.
CONCLUSION:
HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve a pCR after neoadjuvant anthracycline-taxane-based chemotherapy plus anti-HER2 treatment, even if a dual anti-HER2 treatment is given.
AuthorsSibylle Loibl, Gunter von Minckwitz, Andreas Schneeweiss, Stefan Paepke, Annika Lehmann, Mahdi Rezai, Dirk M Zahm, Peter Sinn, Fariba Khandan, Holger Eidtmann, Karel Dohnal, Clemens Heinrichs, Jens Huober, Berit Pfitzner, Peter A Fasching, Fabrice Andre, Judith L Lindner, Christos Sotiriou, August Dykgers, Sanxing Guo, Stephan Gade, Valentina Nekljudova, Sherene Loi, Michael Untch, Carsten Denkert
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 29 Pg. 3212-20 (Oct 10 2014) ISSN: 1527-7755 [Electronic] United States
PMID25199759 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 by American Society of Clinical Oncology.
Chemical References
  • Anthracyclines
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Quinazolines
  • Taxoids
  • Lapatinib
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
Topics
  • Adult
  • Aged
  • Anthracyclines (administration & dosage)
  • Antibodies, Monoclonal, Humanized (administration & dosage)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Biomarkers, Tumor (analysis)
  • Breast Neoplasms (drug therapy, genetics, pathology)
  • Class I Phosphatidylinositol 3-Kinases
  • Exons
  • Female
  • Genotype
  • Humans
  • Lapatinib
  • Middle Aged
  • Mutation
  • Neoadjuvant Therapy
  • Phosphatidylinositol 3-Kinases (genetics)
  • Quinazolines (administration & dosage)
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2 (antagonists & inhibitors, genetics)
  • Taxoids (administration & dosage)
  • Trastuzumab
  • Treatment Outcome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: